Together, these crystal structures illustrate the adaptability of the MeCP2-MBD toward the GTG motif as well as the mCG DNA, and also provide structural basis of a biological role of MeCP2 as a transcription activator and its disease implications in Rett syndrome.
The present study explored various aspects of visual attention of the methyl-CpG-binding protein 2 gene mutant RTT monkeys with the eye-tracking procedure.
Subsequently, we characterized the phenotype of a methyl CpG binding protein 2 (MECP2)-mutant cynomolgus monkey model of Rett syndrome generated using the TALEN approach.
Our study supports the idea that Rett syndrome might arise from simultaneous impairment of cellular processes involving non-overlapping functions of MECP2 isoforms.
With the recent 50th anniversary of the first publication on Rett syndrome, and the almost 20 years since the first report on the link between Rett syndrome and MECP2 mutations, it is important to reflect on the tremendous advances in our understanding and their implications for the diagnosis and treatment of this neurodevelopmental disorder.
While most studies addressed postsynaptic defects in the absence of MeCP2, we took advantage of an <i>in vivo</i> activity-paradigm (seizures), two models of MeCP2 deficiency, and neurobiological assays to reveal novel defects in presynaptic structural plasticity in the hippocampus in RTT rodent models.
Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele.
It appears that there is a sex-dependent effect in X-linked MeCP2-associated disorders, as RTT primarily affects females, whereas MDS is found almost exclusively in males.
Our findings indicate that somatic MECP2 mosaicism contributes directly to the pathogenicity of Rett syndrome, especially in male patients.MECP2-Arg106 might be a mosaic hotspot.
This article reviews the current molecular genetic studies, which investigate the genetic causes of Rett syndrome or Rett-like phenotypes without a MECP2 mutation.
The results confirm that dopaminergic dysfunction in RTT is also present in Mecp2-deficient mice and that reductions in D<sub>2</sub>R more likely explain the impaired ambulation and progressive rigidity observed rather than alterations in DAT.
Rett syndrome (RTT) is a neurodevelopmental disorder mostly caused by mutations in Methyl-CpG-binding protein 2 (MECP2); however, mutations in various other genes may lead to RTT-like phenotypes.
This study investigated the functional relationships between mitochondria and the neuronal differentiation of the MeCP2-deficient stem cells from the exfoliated deciduous teeth of a child with Rett syndrome.
We hypothesized that early-life seizures overactivate these channels, in turn dysregulating Ca<sup>2+</sup>-dependent signaling pathways including that of methyl CPG binding protein 2 (MeCP2), a transcription factor implicated in the autism spectrum disorder (ASD) Rett Syndrome.